PDBsum entry 1ne6

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Hydrolase PDB id
Protein chain
268 a.a. *
SP1 ×2
Waters ×102
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of sp-camp binding r1a subunit of camp- dependent protein kinase
Structure: Camp-dependent protein kinase type i-alpha regulatory chain. Chain: a. Fragment: 1-91 deletion mutant. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Gene: prkar1a. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
2.30Å     R-factor:   0.211     R-free:   0.241
Authors: J.Wu,J.M.Jones,N.H.Xuong,S.S.Taylor
Key ref:
J.Wu et al. (2004). Crystal structures of RIalpha subunit of cyclic adenosine 5'-monophosphate (cAMP)-dependent protein kinase complexed with (Rp)-adenosine 3',5'-cyclic monophosphothioate and (Sp)-adenosine 3',5'-cyclic monophosphothioate, the phosphothioate analogues of cAMP. Biochemistry, 43, 6620-6629. PubMed id: 15157095 DOI: 10.1021/bi0302503
10-Dec-02     Release date:   13-Jan-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00514  (KAP0_BOVIN) -  cAMP-dependent protein kinase type I-alpha regulatory subunit
380 a.a.
268 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cAMP-dependent protein kinase complex   1 term 
  Biological process     regulation of protein phosphorylation   1 term 
  Biochemical function     cAMP-dependent protein kinase regulator activity     1 term  


DOI no: 10.1021/bi0302503 Biochemistry 43:6620-6629 (2004)
PubMed id: 15157095  
Crystal structures of RIalpha subunit of cyclic adenosine 5'-monophosphate (cAMP)-dependent protein kinase complexed with (Rp)-adenosine 3',5'-cyclic monophosphothioate and (Sp)-adenosine 3',5'-cyclic monophosphothioate, the phosphothioate analogues of cAMP.
J.Wu, J.M.Jones, X.Nguyen-Huu, L.F.Ten Eyck, S.S.Taylor.
Cyclic adenosine 5'-monophosphate (cAMP) is an ancient signaling molecule, and in vertebrates, a primary target for cAMP is cAMP-dependent protein kinase (PKA). (R(p))-adenosine 3',5'-cyclic monophosphothioate ((R(p))-cAMPS) and its analogues are the only known competitive inhibitors and antagonists for cAMP activation of PKA, while (S(p))-adenosine 3',5'-cyclic monophosphothioate ((S(p))-cAMPS) functions as an agonist. The crystal structures of a Delta(1-91) deletion mutant of the RIalpha regulatory subunit of PKA bound to (R(p))-cAMPS and (S(p))-cAMPS were determined at 2.4 and 2.3 A resolution, respectively. While the structures are similar to each other and to the crystal structure of RIalpha bound to cAMP, differences in the dynamical properties of the protein when (R(p))-cAMPS is bound are apparent. The structures highlight the critical importance of the exocyclic oxygen's interaction with the invariant arginine in the phosphate binding cassette (PBC) and the importance of this interaction for the dynamical properties of the interactions that radiate out from the PBC. The conformations of the phosphate binding cassettes containing two invariant arginine residues (Arg209 on domain A, and Arg333 on domain B) are somewhat different due to the sulfur interacting with this arginine. Furthermore, the B-site ligand together with the entire domain B show significant differences in their overall dynamic properties in the crystal structure of Delta(1-91) RIalpha complexed with (R(p))-cAMPS phosphothioate analogue ((R(p))-RIalpha) compared to the cAMP- and (S(p))-cAMPS-bound type I and II regulatory subunits, based on the temperature factors. In all structures, two structural solvent molecules exist within the A-site ligand binding pocket; both mediate water-bridged interactions between the ligand and the protein. No structured waters are in the B-site pocket. Owing to the higher resolution data, the N-terminal segment (109-117) of the RIalpha subunit can also be traced. This strand forms an intermolecular antiparallel beta-sheet with the same strand in an adjacent molecule and implies that the RIalpha subunit can form a weak homodimer even in the absence of its dimerization domain.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20018259 C.K.Nickl, S.K.Raidas, H.Zhao, M.Sausbier, P.Ruth, W.Tegge, J.E.Brayden, and W.R.Dostmann (2010).
(D)-Amino acid analogues of DT-2 as highly selective and superior inhibitors of cGMP-dependent protein kinase Ialpha.
  Biochim Biophys Acta, 1804, 524-532.  
21070946 J.Rinaldi, J.Wu, J.Yang, C.Y.Ralston, B.Sankaran, S.Moreno, and S.S.Taylor (2010).
Structure of yeast regulatory subunit: a glimpse into the evolution of PKA signaling.
  Structure, 18, 1471-1482.
PDB code: 3of1
20367611 O.N.Rogacheva, A.V.Popov, E.V.Savvateeva-Popova, V.E.Stefanov, and B.F.Shchegolev (2010).
Thermodynamic analysis of protein kinase A Ialpha activation.
  Biochemistry (Mosc), 75, 233-241.  
19132361 A.V.Nair, C.Anselmi, and M.Mazzolini (2009).
Movements of native C505 during channel gating in CNGA1 channels.
  Eur Biophys J, 38, 465-478.  
18338824 S.Schweinsberg, D.Moll, N.C.Burghardt, C.Hahnefeld, F.Schwede, B.Zimmermann, S.Drewianka, L.Werner, F.Kleinjung, H.G.Genieser, J.Schuchhardt, and F.W.Herberg (2008).
Systematic interpretation of cyclic nucleotide binding studies using KinetXBase.
  Proteomics, 8, 1212-1220.  
17889648 C.Kim, C.Y.Cheng, S.A.Saldanha, and S.S.Taylor (2007).
PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation.
  Cell, 130, 1032-1043.
PDB code: 2qcs
17261079 D.Moll, S.Schweinsberg, C.Hammann, and F.W.Herberg (2007).
Comparative thermodynamic analysis of cyclic nucleotide binding to protein kinase A.
  Biol Chem, 388, 163-172.  
17183361 H.Rehmann, A.Wittinghofer, and J.L.Bos (2007).
Capturing cyclic nucleotides in action: snapshots from crystallographic studies.
  Nat Rev Mol Cell Biol, 8, 63-73.  
17596845 M.Abu-Abed, R.Das, L.Wang, and G.Melacini (2007).
Definition of an electrostatic relay switch critical for the cAMP-dependent activation of protein kinase A as revealed by the D170A mutant of RIalpha.
  Proteins, 69, 112-124.  
17074757 R.Das, and G.Melacini (2007).
A model for agonism and antagonism in an ancient and ubiquitous cAMP-binding domain.
  J Biol Chem, 282, 581-593.  
16322564 D.Vigil, J.H.Lin, C.A.Sotriffer, J.K.Pennypacker, J.A.McCammon, and S.S.Taylor (2006).
A simple electrostatic switch important in the activation of type I protein kinase A by cyclic AMP.
  Protein Sci, 15, 113-121.  
17114296 E.P.Cummins, E.Berra, K.M.Comerford, A.Ginouves, K.T.Fitzgerald, F.Seeballuck, C.Godson, J.E.Nielsen, P.Moynagh, J.Pouyssegur, and C.T.Taylor (2006).
Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity.
  Proc Natl Acad Sci U S A, 103, 18154-18159.  
16207083 C.Hahnefeld, D.Moll, M.Goette, and F.W.Herberg (2005).
Rearrangements in a hydrophobic core region mediate cAMP action in the regulatory subunit of PKA.
  Biol Chem, 386, 623-631.  
15618393 H.M.Berman, L.F.Ten Eyck, D.S.Goodsell, N.M.Haste, A.Kornev, and S.S.Taylor (2005).
The cAMP binding domain: an ancient signaling module.
  Proc Natl Acad Sci U S A, 102, 45-50.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.